Immunocytochemical localization of neurotransmitters at the light and EM level was used to determine the potential functional role of the neurotransmitter in the neural circutry of the medullary and spinal dorsal horn. The opiate peptide enkephalin was shown to modulate the transmission of nociceptive information through synapses on thalamic projection neurons in both laminae I and V. This observation demonstrates that opiates act on post-synaptic receptors, located on thalamic projection neurons. Serotonin immunoreactive axonal endings were identified at the light and EM level. They were found in all laminae of the dorsal horn. In the superficial layers, serotonin axons oriented rostro-caudally. Serotonin endings synapsed mainly on dendrites and occasionally on cell somata. Descending serotonin modulation thus acts predominately through synapess on intrinsic dorsal horn neurons.